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Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes

Primary Purpose

Type 2 Diabetes Mellitus

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

CSII followed by Lina+MET

CSII followed by Lina

CSII followed by MET

CSII alone

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 diabetes mellitus, Continuous subcutaneous insulin infusion, Metformin, Linagliptin

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with type 2 diabetes who have never received any hypoglycemic treatment, or patients with type 2 diabetes <1 year from diagnosis who have used no more than 1 type of hypoglycemic drug for no more than 1 week and discontinued for more than 4 weeks before enrollment;
Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl); glycosylated hemoglobin A1C>8.5%;
Aged between 25 and 65 years, body mass index (BMI) 22-35 kg/m2.

Exclusion Criteria:

Type 1 diabetes or special type of diabetes;
Acute complications of diabetes (including DKA, HHS and lactic acidosis)
Serious microvascular complications: proliferative stage of retinopathy; urine AER >300 mg/g or urine protein positive, quantification >0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy;
Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment;
Persistently increased blood pressure >180/110 mmHg;
Blood creatinine clearance less than 50 ml/min, alanine aminotransferase ≥2.5×upper limit of normal, total bilirubin ≥1.5×upper limit of normal;
Hemoglobin <100 g/L or need regular blood transfusion;
Use of drugs that may influence blood glucose within 12 weeks;
Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;
Uncontrolled endocrine gland dysfunction;
Patients with mental or communication disorders;
Chronic cardiac insufficiency, heart function class III and above;
Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;
Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Sites / Locations

endocrinology department of the first affiliated hospital of Sun Yat-sen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Arm Label

Linagliptin plus metformin

Linagliptin

Metformin

Lifestyle alone

Arm Description

CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks

CSII followed by Linagliptin 5mg Qd for 48 weeks

CSII followed by Metformin 0.5 bid for 48 weeks

No OHA is given after CSII

Outcomes

Primary Outcome Measures

proportion of subjects with optimal glycemic control

proportion of patients achieving glycosylated hemoglobin A1C <7% at the end of sequential treatment in each treatment group.

Secondary Outcome Measures

proportion of subjects with excellent glycemic control

proportion of patients achieving glycosylated hemoglobin A1C <6.5% at the end of sequential treatment in each treatment group.

Change of β cell function

Differences in β-cell indicators among treatment arms at the end of study.

Change of insulin sensitivity

Differences in insulin sensitivity indicators among treatment arms at the end of study.

Incidence of adverse events

Differences in incidence of adverse events among treatment arms at the end of study.

Full Information

NCT ID

NCT03194945

First Posted

June 19, 2017

Last Updated

April 28, 2021

Sponsor

Sun Yat-sen University

Collaborators

Nanfang Hospital, Southern Medical University, Guangdong Provincial People's Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Zhujiang Hospital, Guangzhou First People's Hospital, The Third Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Southern Medical University, Guangdong Provincial Hospital of Traditional Chinese Medicine

1. Study Identification

Unique Protocol Identification Number

NCT03194945

Brief Title

Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes

Official Title

Effects of Linagliptin and Metformin Monotherapy or Combined Sequential Treatment After Early Short-term Intensive Insulin Treatment on Long-term Blood Glucose Control and Function of β Cells in Patients With Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

November 1, 2017 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Short-term intensive insulin therapy(SIIT) is able to reverse β cell dysfunction and induce glycemic remission in patients with newly diagnosed type 2 diabetes. However, proportion of patients with response gradually decreases over time. There is no consensus on which treatment should be given in order to maintain the benefit in glycemic control and β cell recovery. In this multi-center, randomized, controlled study, effects of various sequential treatments ( metformin, linagliptin and combined with both drugs) on long-term blood glucose control as well as preservation of β cell function after SIIT were investigated. In total, 448 patients with newly diagnosed type 2 diabetes who meet the inclusive criteria will be enrolled in eight centers in China. After baseline assessments, all patients will be treated with insulin pump to achieve and maintain euglycemia for 2 weeks. After completion of intensive treatment, insulin pump will be stopped. Different treatments will be applied to patients for 48 weeks according to randomization: Group A: Linagliptin 5 mg Qd + Metformin 0.5 g bid; Group B: Linagliptin 5 mg Qd; Group C: Metformin 0.5 g bid; Group D: No oral drugs. Primary endpoint is proportion of patients achieving glycosylated hemoglobin A1C <7% at the end of the study. Secondary endpoints include proportion of patients achieving glycosylated hemoglobin A1C <6.5% at the end of study; differences in β-cell function , insulin sensitivity, GLP-1 and glucagon secretion among treatment groups, and differences in adverse events among treatment groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes mellitus, Continuous subcutaneous insulin infusion, Metformin, Linagliptin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

448 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Linagliptin plus metformin

Arm Type

Active Comparator

Arm Description

CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks

Arm Title

Linagliptin

Arm Type

Active Comparator

Arm Description

CSII followed by Linagliptin 5mg Qd for 48 weeks

Arm Title

Metformin

Arm Type

Active Comparator

Arm Description

CSII followed by Metformin 0.5 bid for 48 weeks

Arm Title

Lifestyle alone

Arm Type

Active Comparator

Arm Description

No OHA is given after CSII

Intervention Type

Drug

Intervention Name(s)

CSII followed by Lina+MET

Other Intervention Name(s)

CSII+Lina+Met

Intervention Description

short-term intensive CSII followed by Linagliptin 5mg qd and Metformin 0.5g bid for 48 weeks

Intervention Type

Drug

Intervention Name(s)

CSII followed by Lina

Other Intervention Name(s)

CSII+Lina

Intervention Description

short-term intensive CSII followed by Linagliptin 5mg qd for 48 weeks

Intervention Type

Drug

Intervention Name(s)

CSII followed by MET

Other Intervention Name(s)

CSII+Met

Intervention Description

short-term intensive CSII followed by Metformin 0.5g bid for 48 weeks

Intervention Type

Drug

Intervention Name(s)

CSII alone

Other Intervention Name(s)

CSII

Intervention Description

No OHA is given after short-term intensive CSII

Primary Outcome Measure Information:

Title

proportion of subjects with optimal glycemic control

Description

proportion of patients achieving glycosylated hemoglobin A1C <7% at the end of sequential treatment in each treatment group.

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

proportion of subjects with excellent glycemic control

Description

proportion of patients achieving glycosylated hemoglobin A1C <6.5% at the end of sequential treatment in each treatment group.

Time Frame

48 weeks

Title

Change of β cell function

Description

Differences in β-cell indicators among treatment arms at the end of study.

Time Frame

48 weeks

Title

Change of insulin sensitivity

Description

Differences in insulin sensitivity indicators among treatment arms at the end of study.

Time Frame

48 weeks

Title

Incidence of adverse events

Description

Differences in incidence of adverse events among treatment arms at the end of study.

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with type 2 diabetes who have never received any hypoglycemic treatment, or patients with type 2 diabetes <1 year from diagnosis who have used no more than 1 type of hypoglycemic drug for no more than 1 week and discontinued for more than 4 weeks before enrollment; Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl); glycosylated hemoglobin A1C>8.5%; Aged between 25 and 65 years, body mass index (BMI) 22-35 kg/m2. Exclusion Criteria: Type 1 diabetes or special type of diabetes; Acute complications of diabetes (including DKA, HHS and lactic acidosis) Serious microvascular complications: proliferative stage of retinopathy; urine AER >300 mg/g or urine protein positive, quantification >0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy; Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment; Persistently increased blood pressure >180/110 mmHg; Blood creatinine clearance less than 50 ml/min, alanine aminotransferase ≥2.5×upper limit of normal, total bilirubin ≥1.5×upper limit of normal; Hemoglobin <100 g/L or need regular blood transfusion; Use of drugs that may influence blood glucose within 12 weeks; Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea; Uncontrolled endocrine gland dysfunction; Patients with mental or communication disorders; Chronic cardiac insufficiency, heart function class III and above; Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study; Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Liehua Liu, PHD

Phone

+8613751748843

turkey310@163.com

Facility Information:

Facility Name

endocrinology department of the first affiliated hospital of Sun Yat-sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yanbing Li, MD,PhD

Phone

8602087334331

easd04lyb@126.com

First Name & Middle Initial & Last Name & Degree

Yanbing Li, MD,PhD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes

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